A Study of the Immunosuppressive Activity of Methylene Dimethane Sulphonate (MDMS) in Relation to its Effectiveness as an Anti-Tumour Agent

B W Fox,Connie J Gregory

doi:10.1038/bjc.1972.13

Abstract

The anti-tumour action of methylene dimethane sulphonate (MDMS) has been further investigated in relation to its immunosuppressive properties. Following a dose of 10 mg/kg, the proportion of permanent regressions of Yoshida lymphosarcoma transplants is lower in animals treated during the first 5 days of tumour growth. Re-implants on day 28 to those animals in which regression of the tumour had occurred indicated that the immune response to the tumour increases during the first 7 days of tumour growth.Studies of the effect of MDMS on the primary antibody-forming cell response of mice to sheep red cell antigens showed this drug to be an immunosuppressant comparable in strength to x-radiation. MDMS given to rats prior to tumour transplantation also acted as an immunosuppressant in this system resulting in an increased rate of tumour growth. For both responses the maximum immunosuppressive effect was obtained when the interval between drug administration and antigenic challenge was minimal.

Highlights

Studies of the effect of MDMS on the primary antibody-forming cell response of mice to sheep red cell antigens showed this drug to be an immunosuppressant comparable in strength to x-radiation
The results of the present study indicate that the effectiveness of MDMS as an anti-tumour agent varies according to the level of immunity developed in the tumour-bearing host
We have found that MDMS like other members of this series of bifunctional alkylating agents (Berenbaum, Timmis and Brown, 1967) possesses immunosuppressive properties as well as tumour cytotoxicity and the net effect of these two opposing activities in terms of tumour regression, depends on the time of MDMS administration relative to the time of tumour transplantation

Summary

Introduction

Studies of the effect of MDMS on the primary antibody-forming cell response of mice to sheep red cell antigens showed this drug to be an immunosuppressant comparable in strength to x-radiation. MDMS given to rats prior to tumour transplantation acted as an immunosuppressant in this system resulting in an increased rate of tumour growth For both responses the maximum immunosuppressive effect was obtained when the interval between drug administration and antigenic challenge was minimal. METHYLENE dimethane sulphonate (MDMS) has been shown (Fox and Jackson, 1965; Fox, 1969) to exert an excellent anti-tumour action on the transplanted Yoshida lymphosarcoma in the Wistar rat. This tumour is equivalent to an allograft system, but the host reaction against the transplantation antigens, great, does not normally reject the tumour which eventually kills the animal. We have found that MDMS like other members of this series of bifunctional alkylating agents (Berenbaum, Timmis and Brown, 1967) possesses immunosuppressive properties as well as tumour cytotoxicity and the net effect of these two opposing activities in terms of tumour regression, depends on the time of MDMS administration relative to the time of tumour transplantation

Methods

Results

Conclusion